Peracetylation as a Means of Enhancing in Vitro Bioactivity and Bioavailability of Epigallocatechin-3-Gallate

Lambert, Joshua D.; Sang, Shengmin; Hong, Jungil; Kwon, Seok Joo; Lee, Mao Jung; Ho, Chi Tang; Yang, Chung S.

doi:10.1124/dmd.106.011460

Cited by 147 publications

(144 citation statements)

References 18 publications

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“…We have similarly found that in human leukemia Jurkat T cells, Pro-EGCG (1) can also be converted to (À)-EGCG, which was subsequently accumulated. 4 A recent report in which peracetylation increased the bioavailability of (À)-EGCG in esophageal and colon cancer cells (35) substantiates our findings.…”

Section: Discussionsupporting

confidence: 79%

“…This finding provides further evidence for our previous hypothesis that Pro-EGCG (1) behaves as a prodrug form of (À)-EGCG (11). It should be noted that similar levels of (À)-EGCG (50-150 pmol/mg protein) were also recovered from other cultured cell lines after (À)-EGCG treatment (26)(27)(28)(29) and that Pro-EGCG (1) has superior bioavalability over (À)-EGCG (35).…”

Section: Resultsmentioning

confidence: 99%

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A Novel Prodrug of the Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate as a Potential Anticancer Agent

et al. 2007

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Section: Discussionsupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

A Novel Prodrug of the Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate as a Potential Anticancer Agent

et al. 2007

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“…15,16 Acetylation of the phenolic compounds could also favor their absorption, as demonstrated for catechins. 17 Acetylated derivatives of polyphenols can be found in natural sources such as plants. [18][19][20][21] The ability of acetylated polyphenols to promote tumor cell cycle arrest, death and to sensitize them to other anticancer agents remained to be explored.…”

mentioning

confidence: 99%

Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro‐uracil sensitivity in human derived colon cancer cells

Colin

Gimazane

Lizard

et al. 2009

Intl Journal of Cancer

115

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Epidemiological studies suggested that trans-resveratrol, a wine grape component, could prevent malignant tumor development. This compound also demonstrated cytostatic and cytotoxic effects on tumor cells in vitro. To obtain trans-resveratrol derivatives with a better cellular uptake and enhanced antiproliferative effects, we synthesized a triacetate derivative as well as an oligomer, e-viniferin and its acetylated form, e-viniferin penta-acetate. We also obtained vineatrol, a wine grape shoot extract that associates several polyphenols that may act synergistically, including trans-resveratrol and e-viniferin. We show here that resveratrol triacetate and vineatrol are as efficient as trans-resveratrol in inducing the accumulation of human colon cancer cells in early S phase of the cell cycle. This effect is associated with a nuclear redistribution of cyclin A and the formation of a cyclin A/cyclindependent kinase 2 complex whose kinase activity is increased. In contrast, e-viniferin and its acetylated form do not demonstrate any significant activity on these cells when tested alone. Interestingly, resveratrol triacetate and vineatrol dramatically enhance 5-Fluoro-Uracil-mediated inhibition of colon cancer cell proliferation. Thus, acetylated derivatives of resveratrol have retained the cytostatic and cytotoxic activities of the parental molecule and thus deserve to be tested as chemosensitizers in animal models. ' UICCKey words: colon cancer; cell cycle; polyphenols; resveratrol; vineatrol; chemosensitization Epidemiological studies suggested that the polyphenol resveratrol (trans-3,4 0 ,5-trihydroxystilbene) was one of the main wine grape components that protect from vascular diseases, neurodegenerative processes and cancers. 1 The ability of resveratrol to prevent the occurrence of carcinomas was related to the inhibition of tumor cell cycle 2,3 and induction of tumor cell death. 4,5 In addition, there is compelling in vitro evidence that trans-resveratrol behaves as a chemosensitizer when combined with cytotoxic drugs, 6 cytokines 7 and other polyphenols such as quercetin, apigenin and genistein. 8,9 Resveratrol is probably not the only bioactive compound present in the grape wine. Oligomers of resveratrol such as viniferins, were suggested to block the proliferation of several tumoral cell lines 10-12 and a vineatrol preparation containing both trans-resveratrol and e-viniferin exhibited a greater antiproliferative effect on malignant cell lines than each compound tested separately. 13,14 Lipophilic derivatives were obtained through esterification of the hydroxyl functions with aliphatic molecules, which improved their intestinal absorption and cell penetration. 15,16 Acetylation of the phenolic compounds could also favor their absorption, as demonstrated for catechins. 17 Acetylated derivatives of polyphenols can be found in natural sources such as plants. [18][19][20][21] The ability of acetylated polyphenols to promote tumor cell cycle arrest, death and to sensitize them to other anticancer agents remai...

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“…(-) Epicatechin 3-gallate (11) has low bioavailability due to extensive metabolism and instability in medium and alkaline pH conditions. Structural changes can improve the physicochemical biotransformation (Lambert et al, 2006). A more sophisticated strategy proposes the transformation of the phenolic substances into a pro-drug, which is associated with a nanoformulation.…”

Section: Pro-drugsmentioning

confidence: 99%

“…properties and avoid a rapid metabolization. Studies led to peracetylation of catechins to enhance the hydrophobicity and make hydroxyl groups unavailable for biotransformation (Lambert et al, 2006). A more sophisticated strategy proposes the transformation of the phenolic substances into a pro-drug, which is associated with a nanoformulation.…”

Section: Pro-drugsmentioning

confidence: 99%

Biodisponibilidade de compostos fenólicos: um importante desafio para o desenvolvimento de fármacos?

Souza¹,

Casanova²,

Costa³

2014

Revista Fitos

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ResumoAs substâncias fenólicas constituem uma importante classe de metabólitos secundários, amplamente distribuídas no reino vegetal. Diversas atividades biológicas in vitro são atribuídas a essa classe de substâncias. Entretanto, algumas dessas substâncias não apresentam o mesmo perfil de atividade nos ensaios in vivo. Parte disso pode ser explicada pela baixa biodisponibilidade dessas substâncias. As principais razões encontradas para este fato podem ser a baixa solubilidade em meio aquoso, a fraca estabilidade gastrointestinal, a dificuldade em atravessar membranas e a rápida e extensa metabolização. Os metabólitos produzidos na biotransformação pela microbiota intestinal e por enzimas hepáticas poderiam explicar a baixa eficácia dessas substâncias. Em contrapartida, a biotransformação também pode originar metabólitos potencialmente mais ativos que as substâncias originais. Diante da relevância do tema, este artigo tem como objetivo abordar os impactos da metabolização das substâncias fenólicas sobre o efeito farmacológico. Adicionalmente, serão apresentadas estratégias que podem ser utilizadas para aumentar a bioeficácia dessas substâncias, e consequentemente, contribuir para o aproveitamento dessa classe química no desenvolvimento de fármacos de origem vegetal.Palavras-chave: Substâncias fenólicas; atividades biológicas; metabolismo; biodisponibilidade; formulações; pró-drogas. AbstractPhenolic substances are an important class of secondary metabolites widely distributed in the plant kingdom. Several biological activities in vitro are assigned to this class of substances. However, some of these substances do not have the same profile of activity in in vivo assays. This fact could be partially explained by the low bioavailability of these substances. The main reasons for this low bioavailability may be low aqueous solubility, poor gastrointestinal stability and difficulty crossing membranes. The rapid and extensive metabolism by the intestinal flora and by some liver enzymes of phenolic substances after oral administration, may explain the poor bioavailability. In contrast, biotransformation can also lead to metabolites potentially more active than the original substances. Given the importance of the topic, this article aims to address the impacts of metabolism of phenolic substances on their pharmacological effects. Additionally, we show strategies to improve the bioefficacy of these substances, contributing to their use in the development of drugs of vegetal origin.

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Peracetylation as a Means of Enhancing in Vitro Bioactivity and Bioavailability of Epigallocatechin-3-Gallate

Cited by 147 publications

References 18 publications

A Novel Prodrug of the Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate as a Potential Anticancer Agent

A Novel Prodrug of the Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate as a Potential Anticancer Agent

Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro‐uracil sensitivity in human derived colon cancer cells

Biodisponibilidade de compostos fenólicos: um importante desafio para o desenvolvimento de fármacos?

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